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针对阿尔茨海默病的糖原合成酶激酶-3β:最近的进展和未来的前景

Zimeng Cheng¹, Tianyue Han¹, Jingtong Yao¹

¹Department of Medical Pharmacy, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong, People's Republic of China.

European journal of medicinal chemistry

|December 31, 2023

概括

糖原合成酶激酶-3β (GSK-3β) 抑制剂通过向神经纤维状结,对阿尔茨海默病 (AD) 治疗具有前景. 最近的研究审查了各种抑制剂,很少有进展到临床试验,突出了安全和有效治疗的需要.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
生物化学生物化学

背景情况:

阿尔茨海默病 (AD) 的特点是粉样斑块和神经纤维状结 (NFT).
糖原合成酶激酶-3β (GSK-3β) 与NFT形成有关,并且在AD大脑中高度表达.
抑制GSK-3β是一种潜在的治疗策略.

研究的目的:

综合审查在过去五年中为阿尔茨海默病治疗开发的GSK-3β抑制剂.
分析不同类型的GSK-3β抑制剂,包括ATP竞争性,非ATP竞争性,和全抑制剂.
探索解决各种AD假设的多目标定向带 (MTDLs).

主要方法:

在过去五年中发表的GSK-3β抑制剂的文献综述.
基于其作用机制和目标参与的抑制剂的分析.
对已进入AD临床试验的化合物的评估.

主要成果:

已经确定了多种GSK-3β抑制剂,具有不同的作用机制.
只有碳酸和提德格卢西布已经达到阿尔茨海默病的临床试验.
对类,全类和多功能抑制剂的兴趣日益增加,这些抑制剂针对多个AD途径.

结论:

抑制GSK-3β仍然是AD治疗的一个有希望的途径.
需要进一步开发以确定安全有效的GSK-3β抑制剂.
MTDLs提供了一个潜在的策略来解决阿尔茨海默病的复杂性.

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